Hepatitis C virus (HCV) is thought to be involved in the pathogenesis of autoimmune hepatitis (AIH) type 2, which is defined by the presence of type I antiliver kidney microsome autoantibodies directed mainly against cytochrome P450 (CYP)2D6 and by autoreactive liver infiltrating T cells. Virus-specific CD8(+) cytotoxic T lymphocytes (CTLs) that recognize infected cells and contribute to viral ...

Vorozole and letrozole are third-generation aromatase (cytochrome P450 19A1) inhibitors. [(11)C]-Vorozole can be used as a radiotracer for aromatase in living animals but when administered by IV, it collects in the liver. Pretreatment with letrozole does not affect the binding of vorozole in the liver. In search of finding the protein responsible for the accumulation of vorozole in the liver, f...

The cytochrome P450 (P450, CYP) are the superfamily of heme-containing monooxygenase enzymes, found throughout all nature including mammals, plants, and microorganisms. Mammalian P450 enzymes are involved in oxidative metabolism of a wide range of endo- and exogenous chemicals. Especially P450s involved in drug metabolisms are important for drug efficacy and polymorphisms of P450s in individual...

Genetic polymorphisms of enzymes involved in the metabolism of carcinogens are suggested to modify an individual's susceptibility to lung cancer. The purpose of this study was to investigate the relationship between lung cancer cases in Japan and variant alleles of cytochrome P450 (CYP) 2A6 (CYP2A6*4), CYP2A13 (CYP2A13*1-*10), CYP4B1 (CYP4B1*1-*7), sulfotransferase 1A1 (SULT1A1*2), glutathione ...

The effects of methanol, ethanol, dimethyl sulfoxide (DMSO), and acetonitrile were studied in vitro on nine individual, cDNAexpressed cytochrome P-450 activities (phenacetin O-deethylase for CYP1A1 and CYP1A2, coumarin 7-hydroxylase for CYP2A6, testosterone 6beta-hydroxylase for CYP3A4, 7-ethoxy-4-trifluoromethylcoumarin deethylase for CYP2B6, paclitaxel 6alpha-hydroxylase for CYP2C8, diclofena...

The whole gene deletion CYP2A6*4, the defect of the main nicotine oxidase, contributes to limiting lifelong and daily cigarette consumption. However, the effects on smoking habits of CYP2A6*7 and *9, two major functional polymorphisms common in Asian populations, have not been reported. The present study examined the relationship between polymorphisms *4, *7 and *9 with the smoking habits of 20...

Cytochrome P450 2A13 (CYP2A13), an enzyme expressed predominantly in the human respiratory tract, exhibits high efficiency in the metabolic activation of tobacco carcinogen 4-(methylnitrosamino)-1-(3pyridyl)-1-butanone (NNK). A C3T transition in the CYP2A13 gene causes Arg257Cys amino acid substitution and, thus, results in a significantly reduced activity toward NNK and other substrates. In th...

Human CYP2A6 has been recognized as being involved in the mutagenic activation of promutagens such as the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Methoxsalen (8-methoxypsoralen) was reported to inhibit CYP2A6. In the present study, the inhibitory effects of methoxsalen on NNK-induced lung tumorigenesis in female A/J mice were examined. Female A/J mice...

The age-standardized incidence of esophageal cancer (EC) varies from 3 to >100/100,000 per year in different provinces of Iran. This striking variation of incidence is associated with differences in ethnic backgrounds, raising the possibility that genetic factors are involved in the pathogenesis of EC. We compared the frequencies of polymorphisms in ten genes that have been hypothesized to have...